NO792696L - MENOCARBOXYLATES OF PHENYLGUANIDIC ACID ESTERS AND PROCEDURES FOR THEIR PREPARATION - Google Patents
MENOCARBOXYLATES OF PHENYLGUANIDIC ACID ESTERS AND PROCEDURES FOR THEIR PREPARATIONInfo
- Publication number
- NO792696L NO792696L NO792696A NO792696A NO792696L NO 792696 L NO792696 L NO 792696L NO 792696 A NO792696 A NO 792696A NO 792696 A NO792696 A NO 792696A NO 792696 L NO792696 L NO 792696L
- Authority
- NO
- Norway
- Prior art keywords
- formula
- methoxycarbonyl
- phenyl
- guanidine
- alkyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 17
- 239000002253 acid Substances 0.000 title claims description 5
- 238000002360 preparation method Methods 0.000 title description 6
- -1 phenylguanidine sulfonic acid esters Chemical class 0.000 claims description 42
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000004432 carbon atom Chemical group C* 0.000 claims description 28
- 150000001875 compounds Chemical class 0.000 claims description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims description 17
- 239000001257 hydrogen Substances 0.000 claims description 17
- 150000002431 hydrogen Chemical class 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 10
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- 150000007522 mineralic acids Chemical class 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 6
- 150000003839 salts Chemical class 0.000 claims description 6
- QRJZGVVKGFIGLI-UHFFFAOYSA-N 2-phenylguanidine Chemical compound NC(=N)NC1=CC=CC=C1 QRJZGVVKGFIGLI-UHFFFAOYSA-N 0.000 claims description 5
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 5
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000005415 substituted alkoxy group Chemical group 0.000 claims description 4
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 4
- 244000000013 helminth Species 0.000 claims description 3
- 150000002541 isothioureas Chemical class 0.000 claims description 3
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- RMAHPRNLQIRHIJ-UHFFFAOYSA-N methyl carbamimidate Chemical class COC(N)=N RMAHPRNLQIRHIJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000002490 anilino group Chemical class [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
- 229940126601 medicinal product Drugs 0.000 claims 1
- 210000000056 organ Anatomy 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 8
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 6
- 241000545744 Hirudinea Species 0.000 description 6
- 238000006243 chemical reaction Methods 0.000 description 6
- 239000000460 chlorine Substances 0.000 description 6
- 229910052801 chlorine Inorganic materials 0.000 description 6
- 229910052731 fluorine Inorganic materials 0.000 description 6
- 239000011737 fluorine Substances 0.000 description 6
- 210000004185 liver Anatomy 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 241000244206 Nematoda Species 0.000 description 5
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 5
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 5
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
- BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 4
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- 229960000583 acetic acid Drugs 0.000 description 4
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 235000011121 sodium hydroxide Nutrition 0.000 description 4
- 239000007858 starting material Substances 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 4
- 241000283690 Bos taurus Species 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- 241000283086 Equidae Species 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 230000000507 anthelmentic effect Effects 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
- 229910052794 bromium Inorganic materials 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 3
- 239000000706 filtrate Substances 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 238000006460 hydrolysis reaction Methods 0.000 description 3
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 241000282887 Suidae Species 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- PEOUQUKUHBWKGO-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl] 4-amino-3-nitrobenzenesulfonate Chemical compound C1=C([N+]([O-])=O)C(N)=CC=C1S(=O)(=O)OC1=CC=CC(C(F)(F)F)=C1 PEOUQUKUHBWKGO-UHFFFAOYSA-N 0.000 description 2
- DOCSUTOJBMLNFH-UHFFFAOYSA-N [3-[(n-methoxycarbonyl-n'-methylcarbamimidoyl)amino]-4-(propanoylamino)phenyl] benzenesulfonate Chemical compound C1=C(NC(NC(=O)OC)=NC)C(NC(=O)CC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 DOCSUTOJBMLNFH-UHFFFAOYSA-N 0.000 description 2
- MNRWLAGBOWNDOE-UHFFFAOYSA-N [3-[2-(2-methoxyacetyl)hydrazinyl]phenyl] benzenesulfonate Chemical compound COCC(=O)NNC1=CC=CC(OS(=O)(=O)C=2C=CC=CC=2)=C1 MNRWLAGBOWNDOE-UHFFFAOYSA-N 0.000 description 2
- QSHNOLMLGJKXGB-UHFFFAOYSA-N [4-formamido-3-[(n-methoxycarbonyl-n'-methylcarbamimidoyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(NC=O)C(NC(NC(=O)OC)=NC)=CC(OS(=O)(=O)C=2C=CC=CC=2)=C1 QSHNOLMLGJKXGB-UHFFFAOYSA-N 0.000 description 2
- RHDZSFLIWVFNOW-UHFFFAOYSA-N [carbamoyl(methyl)amino] methyl carbonate Chemical compound C(=O)(OC)ON(C(O)=N)C RHDZSFLIWVFNOW-UHFFFAOYSA-N 0.000 description 2
- 229960001413 acetanilide Drugs 0.000 description 2
- 239000013543 active substance Substances 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 150000003840 hydrochlorides Chemical class 0.000 description 2
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 2
- MMBDAJMDNVQFDV-UHFFFAOYSA-N methyl n-[amino(methylsulfanyl)methylidene]carbamate Chemical compound COC(=O)N=C(N)SC MMBDAJMDNVQFDV-UHFFFAOYSA-N 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- QGRNOSUTWZYDTP-UHFFFAOYSA-N (2-chlorophenyl) 4-acetamido-3-[(n'-methoxycarbonylcarbamimidoyl)amino]benzenesulfonate Chemical compound C1=C(NC(C)=O)C(NC(=N)NC(=O)OC)=CC(S(=O)(=O)OC=2C(=CC=CC=2)Cl)=C1 QGRNOSUTWZYDTP-UHFFFAOYSA-N 0.000 description 1
- OQLVOYMTVSGURZ-UHFFFAOYSA-N (3-chlorophenyl) 4-acetamido-3-[(n'-methoxycarbonylcarbamimidoyl)amino]benzenesulfonate Chemical compound C1=C(NC(C)=O)C(NC(=N)NC(=O)OC)=CC(S(=O)(=O)OC=2C=C(Cl)C=CC=2)=C1 OQLVOYMTVSGURZ-UHFFFAOYSA-N 0.000 description 1
- ZVYDMTNZGWUXFR-UHFFFAOYSA-N (3-ethoxyphenyl) 3-[[amino-(methoxycarbonylamino)methylidene]amino]-4-[(2-methoxyacetyl)amino]benzenesulfonate Chemical compound CCOC1=CC=CC(OS(=O)(=O)C=2C=C(N\C(N)=N\C(=O)OC)C(NC(=O)COC)=CC=2)=C1 ZVYDMTNZGWUXFR-UHFFFAOYSA-N 0.000 description 1
- BCKMKZCGVQENKO-UHFFFAOYSA-N (4-cyanophenyl) 4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1S(=O)(=O)OC1=CC=C(C#N)C=C1 BCKMKZCGVQENKO-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- KWCPQPFOPUCWPH-UHFFFAOYSA-N 1-(oxomethylidene)guanidine Chemical compound NC(=N)N=C=O KWCPQPFOPUCWPH-UHFFFAOYSA-N 0.000 description 1
- GEGLCBTXYBXOJA-UHFFFAOYSA-N 1-methoxyethanol Chemical compound COC(C)O GEGLCBTXYBXOJA-UHFFFAOYSA-N 0.000 description 1
- WEYSQARHSRZNTC-UHFFFAOYSA-N 1h-benzimidazol-2-ylcarbamic acid Chemical class C1=CC=C2NC(NC(=O)O)=NC2=C1 WEYSQARHSRZNTC-UHFFFAOYSA-N 0.000 description 1
- BHFLSZOGGDDWQM-UHFFFAOYSA-N 1h-benzimidazole;carbamic acid Chemical class NC(O)=O.C1=CC=C2NC=NC2=C1 BHFLSZOGGDDWQM-UHFFFAOYSA-N 0.000 description 1
- SADHVOSOZBAAGL-UHFFFAOYSA-N 3-(trifluoromethoxy)aniline Chemical compound NC1=CC=CC(OC(F)(F)F)=C1 SADHVOSOZBAAGL-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- 241000893172 Chabertia Species 0.000 description 1
- 241001126268 Cooperia Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000243976 Haemonchus Species 0.000 description 1
- 241000920462 Heterakis Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- YRWLZFXJFBZBEY-UHFFFAOYSA-N N-(6-butyl-1H-benzimidazol-2-yl)carbamic acid methyl ester Chemical compound CCCCC1=CC=C2N=C(NC(=O)OC)NC2=C1 YRWLZFXJFBZBEY-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 241000510960 Oesophagostomum Species 0.000 description 1
- 241000243795 Ostertagia Species 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000030852 Parasitic disease Diseases 0.000 description 1
- 241001494479 Pecora Species 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical class CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 241000282849 Ruminantia Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 241000244174 Strongyloides Species 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241000242541 Trematoda Species 0.000 description 1
- 241000243797 Trichostrongylus Species 0.000 description 1
- TWELYPUFCLUBML-UHFFFAOYSA-N [3-(2-methylpropoxy)phenyl] 4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1S(=O)(=O)OC1=CC=CC(OCC(C)C)=C1 TWELYPUFCLUBML-UHFFFAOYSA-N 0.000 description 1
- AUNRIVCUEICHNU-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl] 4-(butanoylamino)-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)CCC)=CC=C1S(=O)(=O)OC1=CC=CC(C(F)(F)F)=C1 AUNRIVCUEICHNU-UHFFFAOYSA-N 0.000 description 1
- QRLSALSSWXAEJB-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl] 4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1S(=O)(=O)OC1=CC=CC(C(F)(F)F)=C1 QRLSALSSWXAEJB-UHFFFAOYSA-N 0.000 description 1
- LJNJJEMEHCBZQQ-UHFFFAOYSA-N [3-(trifluoromethyl)phenyl] 4-chloro-3-nitrobenzenesulfonate Chemical compound C1=C(Cl)C([N+](=O)[O-])=CC(S(=O)(=O)OC=2C=C(C=CC=2)C(F)(F)F)=C1 LJNJJEMEHCBZQQ-UHFFFAOYSA-N 0.000 description 1
- GWBSILSTUTUSGM-UHFFFAOYSA-N [3-[(N'-ethyl-N-methoxycarbonylcarbamimidoyl)amino]-4-[(2-methoxyacetyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(=O)COC)C(NC(NC(=O)OC)=NCC)=CC(OS(=O)(=O)C=2C=CC=CC=2)=C1 GWBSILSTUTUSGM-UHFFFAOYSA-N 0.000 description 1
- UPTWTJUIAGWTBP-UHFFFAOYSA-N [3-[(n'-benzyl-n-methoxycarbonylcarbamimidoyl)amino]-4-[(2-methoxyacetyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(NC(=O)OC)=NCC=2C=CC=CC=2)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 UPTWTJUIAGWTBP-UHFFFAOYSA-N 0.000 description 1
- DYALAEHIWFZFKL-UHFFFAOYSA-N [3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]-4-(pentanoylamino)phenyl] benzenesulfonate Chemical compound C1=C(NC(=N)NC(=O)OC)C(NC(=O)CCCC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 DYALAEHIWFZFKL-UHFFFAOYSA-N 0.000 description 1
- QMUPLEHOHBUTHM-UHFFFAOYSA-N [3-[bis(methoxycarbonylamino)methylideneamino]-4-[(2-methoxyacetyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(N\C(NC(=O)OC)=N\C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 QMUPLEHOHBUTHM-UHFFFAOYSA-N 0.000 description 1
- FOLKNFXXHSKYJY-UHFFFAOYSA-N [4-(butanoylamino)-3-[(n-methoxycarbonyl-n'-methylcarbamimidoyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(NC(=O)OC)=NC)C(NC(=O)CCC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 FOLKNFXXHSKYJY-UHFFFAOYSA-N 0.000 description 1
- IDFGSVLIZIXOET-UHFFFAOYSA-N [4-(butanoylamino)-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(=N)NC(=O)OC)C(NC(=O)CCC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 IDFGSVLIZIXOET-UHFFFAOYSA-N 0.000 description 1
- ABSAIOOLAAECTK-UHFFFAOYSA-N [4-(hexanoylamino)-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(=N)NC(=O)OC)C(NC(=O)CCCCC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 ABSAIOOLAAECTK-UHFFFAOYSA-N 0.000 description 1
- YUYMYANYNVLLBW-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[(n'-methoxycarbonylcarbamimidoyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC=C1 YUYMYANYNVLLBW-UHFFFAOYSA-N 0.000 description 1
- LSAQGPKXLWRUGT-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] 3-(2-methylpropoxy)benzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC(OCC(C)C)=C1 LSAQGPKXLWRUGT-UHFFFAOYSA-N 0.000 description 1
- SDPFRUQGUODQOX-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] 3-chloro-4-methylbenzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=C(C)C(Cl)=C1 SDPFRUQGUODQOX-UHFFFAOYSA-N 0.000 description 1
- IOARJLPLSGAIGG-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] 3-methoxybenzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC(OC)=C1 IOARJLPLSGAIGG-UHFFFAOYSA-N 0.000 description 1
- KLJCYFNEAWWWFY-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] 3-propan-2-yloxybenzenesulfonate Chemical compound C1=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=C1OS(=O)(=O)C1=CC=CC(OC(C)C)=C1 KLJCYFNEAWWWFY-UHFFFAOYSA-N 0.000 description 1
- WRXCMINGXAVONE-UHFFFAOYSA-N [4-[(2-methoxyacetyl)amino]-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]phenyl] 3-propoxybenzenesulfonate Chemical compound CCCOC1=CC=CC(S(=O)(=O)OC=2C=C(N\C(N)=N/C(=O)OC)C(NC(=O)COC)=CC=2)=C1 WRXCMINGXAVONE-UHFFFAOYSA-N 0.000 description 1
- PSEVLPBSVNCJCN-UHFFFAOYSA-N [4-acetamido-3-[(n-methoxycarbonyl-n'-methylcarbamimidoyl)amino]phenyl] benzenesulfonate Chemical compound C1=C(NC(C)=O)C(NC(NC(=O)OC)=NC)=CC(OS(=O)(=O)C=2C=CC=CC=2)=C1 PSEVLPBSVNCJCN-UHFFFAOYSA-N 0.000 description 1
- 150000001242 acetic acid derivatives Chemical class 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 229940124339 anthelmintic agent Drugs 0.000 description 1
- 239000000921 anthelmintic agent Substances 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000003776 cleavage reaction Methods 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000008298 dragée Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
- 125000005745 ethoxymethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229960005473 fenbendazole Drugs 0.000 description 1
- IRHZVMHXVHSMKB-UHFFFAOYSA-N fenbendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1SC1=CC=CC=C1 IRHZVMHXVHSMKB-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical class [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 125000001188 haloalkyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 150000003893 lactate salts Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- BAXLBXFAUKGCDY-UHFFFAOYSA-N mebendazole Chemical compound [CH]1C2=NC(NC(=O)OC)=NC2=CC=C1C(=O)C1=CC=CC=C1 BAXLBXFAUKGCDY-UHFFFAOYSA-N 0.000 description 1
- 229960003439 mebendazole Drugs 0.000 description 1
- BPQPMIVFFHJAMW-UHFFFAOYSA-N methyl (ne)-n-[amino-[2-[(2-methoxyacetyl)amino]-5-phenoxyanilino]methylidene]carbamate Chemical compound C1=C(NC(N)=NC(=O)OC)C(NC(=O)COC)=CC=C1OC1=CC=CC=C1 BPQPMIVFFHJAMW-UHFFFAOYSA-N 0.000 description 1
- CTTQZMFVWLLLCK-UHFFFAOYSA-N methyl N-(N'-methylcarbamimidoyl)carbamate Chemical compound COC(=O)NC(N)=NC CTTQZMFVWLLLCK-UHFFFAOYSA-N 0.000 description 1
- PYYOLLJLOKSVNW-UHFFFAOYSA-N methyl N-[C-methylsulfanyl-N-(1-phenylethyl)carbonimidoyl]carbamate Chemical compound COC(=O)NC(SC)=NC(C)C1=CC=CC=C1 PYYOLLJLOKSVNW-UHFFFAOYSA-N 0.000 description 1
- PAVDBWFMFPEZIE-UHFFFAOYSA-N methyl n-(diaminomethylidene)carbamate Chemical compound COC(=O)NC(N)=N PAVDBWFMFPEZIE-UHFFFAOYSA-N 0.000 description 1
- ZVQWOWXQCUFSCA-UHFFFAOYSA-N methyl n-(n-butyl-c-methylsulfanylcarbonimidoyl)carbamate Chemical compound CCCCN=C(SC)NC(=O)OC ZVQWOWXQCUFSCA-UHFFFAOYSA-N 0.000 description 1
- YOHHRGBAXFZGRV-UHFFFAOYSA-N methyl n-(n-ethyl-c-methylsulfanylcarbonimidoyl)carbamate Chemical compound CCN=C(SC)NC(=O)OC YOHHRGBAXFZGRV-UHFFFAOYSA-N 0.000 description 1
- MVLWYBBNGYTKJB-UHFFFAOYSA-N methyl n-[n-(cyclohexylmethyl)-c-methylsulfanylcarbonimidoyl]carbamate Chemical compound COC(=O)NC(SC)=NCC1CCCCC1 MVLWYBBNGYTKJB-UHFFFAOYSA-N 0.000 description 1
- MZGCLZOJWGVQGX-UHFFFAOYSA-N methyl n-carbamimidoyl-n-phenylcarbamate Chemical class COC(=O)N(C(N)=N)C1=CC=CC=C1 MZGCLZOJWGVQGX-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- YZMHQCWXYHARLS-UHFFFAOYSA-N naphthalene-1,2-disulfonic acid Chemical class C1=CC=CC2=C(S(O)(=O)=O)C(S(=O)(=O)O)=CC=C21 YZMHQCWXYHARLS-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 229950007337 parbendazole Drugs 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- HIYSRSZBCNBQSY-UHFFFAOYSA-N phenyl 3-[(n'-butyl-n-methoxycarbonylcarbamimidoyl)amino]-4-[(2-methoxyacetyl)amino]benzenesulfonate Chemical compound C1=C(NC(=O)COC)C(NC(NC(=O)OC)=NCCCC)=CC(S(=O)(=O)OC=2C=CC=CC=2)=C1 HIYSRSZBCNBQSY-UHFFFAOYSA-N 0.000 description 1
- LAZBFXGTLDXAJE-UHFFFAOYSA-N phenyl 4-(hexanoylamino)-3-[[(e)-n'-methoxycarbonylcarbamimidoyl]amino]benzenesulfonate Chemical compound C1=C(NC(=N)NC(=O)OC)C(NC(=O)CCCCC)=CC=C1S(=O)(=O)OC1=CC=CC=C1 LAZBFXGTLDXAJE-UHFFFAOYSA-N 0.000 description 1
- HDRHWXNZPUTFLK-UHFFFAOYSA-N phenyl 4-[(2-methoxyacetyl)amino]-3-[(n-methoxycarbonyl-n'-methylcarbamimidoyl)amino]benzenesulfonate Chemical compound C1=C(NC(NC(=O)OC)=NC)C(NC(=O)COC)=CC=C1S(=O)(=O)OC1=CC=CC=C1 HDRHWXNZPUTFLK-UHFFFAOYSA-N 0.000 description 1
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 description 1
- 235000021317 phosphate Nutrition 0.000 description 1
- 150000003013 phosphoric acid derivatives Chemical class 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 125000000020 sulfo group Chemical group O=S(=O)([*])O[H] 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 150000003467 sulfuric acid derivatives Chemical class 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 description 1
- 239000000052 vinegar Substances 0.000 description 1
- 235000021419 vinegar Nutrition 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/75—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing singly-bound oxygen atoms bound to the carbon skeleton
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
- C07C309/72—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C309/73—Esters of sulfonic acids having sulfur atoms of esterified sulfo groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
- C07C2601/14—The ring being saturated
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Tropical Medicine & Parasitology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Description
Monokarboksylater av fenylguanidinsulfonsyreestere, fremgangsmåte til deres fremstilling og deres anvendelse som legemiddel. Monocarboxylates of phenylguanidine sulfonic acid esters, process for their preparation and their use as medicine.
Det er kjent at fenylguanidiner med formel:, It is known that phenylguanidines of formula:,
hvori R betyr lavere alkyl, R' betyr lavere-alkyl eller hydrogen og R" betyr -C4Hg, -COCgH5, -OCgH5 eller -SC6H5er antelmintisk virksomme (sml. DOS 21 17 293, 22 50 911, 23 04 764 og 24 23 679). in which R means lower alkyl, R' means lower alkyl or hydrogen and R" means -C4Hg, -COCgH5, -OCgH5 or -SC6H5 are anthelminthically active (cf. DOS 21 17 293, 22 50 911, 23 04 764 and 24 23 679 ).
Disse fenylguanidiner og også antelminthica fra klassen benzimidazol-2-karbaminater, som parbendazol, mebendazol, fenbendazol og andre representater for denne stoffklasse er tungt oppløselig i vann og kan derfor bare appliseres oralt'i human- These phenylguanidines and also anthelminthica from the class of benzimidazole-2-carbamates, such as parbendazole, mebendazole, fenbendazole and other representatives of this substance class are poorly soluble in water and can therefore only be applied orally in humans
og veterinærmedisinen. Med disse stoffer lar det seg ikke uten videre fremstille parenteralt anvendbare,lokalt godt tålbare opp-løsninger, slik de spesielt kreves for behandling av store dyr som storfe, hester og svin. and veterinary medicine. With these substances, it is not possible to easily prepare parenterally applicable, locally well-tolerated solutions, as they are particularly required for the treatment of large animals such as cattle, horses and pigs.
Videre er det ifølge DOS 26 30 847 kjent metoksy-karbonylfenylguanidiner med formel: Furthermore, according to DOS 26 30 847, methoxy-carbonylphenylguanidines are known with the formula:
hvori X betyr oksygen, svovel, -SO-, -SO^- eller -CO-gruppen og wherein X means oxygen, sulfur, the -SO-, -SO^- or -CO group and
hvori X i stilling 4 eller 5 er forbundet med fenylguanidino-resten, R betyr hydrogen, halogen, alkoksy-(C-^-C^) eller trifluormetyl, R^" betyr hydrogen, eventuelt substituert alkyl, eventuelt, substituert alkoksy, eventuelt substituert alkoksyalkyl, wherein X in position 4 or 5 is connected to the phenylguanidino residue, R means hydrogen, halogen, alkoxy-(C-^-C^) or trifluoromethyl, R^" means hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted alkoxyalkyl,
2 2
eventuelt substituert aralkyl, R betyr hydrogen, alkyl, cykloalkyl, cykloalkylalkyl eller aralkyl, hvis salter med uorganiske eller organiske syrer er oppløselig i vann og dermed anvendbare parenteralt. De virker riktignok mot et bredt spektrum av nematoder, imidlertid ikke tilstrekkelig overfor leverigler, en parasitt som ofte forekommer sammen med nematoden i mave-tarm-kanalen,, og hensiktsmessig bekjempes sammen med nematodene. optionally substituted aralkyl, R means hydrogen, alkyl, cycloalkyl, cycloalkylalkyl or aralkyl, whose salts with inorganic or organic acids are soluble in water and thus usable parenterally. They do indeed work against a broad spectrum of nematodes, but not sufficiently against liver leeches, a parasite that often occurs together with the nematode in the gastrointestinal tract, and is appropriately combated together with the nematodes.
Ifølge DOS 24 41 201 og 24 41 202 er det riktignok kjent benzimi-dazolkarbaminater med formel According to DOS 24 41 201 and 24 41 202, it is true that benzimidazole carbamates with the formula
hvori X betyr gruppen -OSO2- eller -SO2O-, R betyr alkyl med 1 til 4 C-atomer, R<1>og R" betyr hver uavhengig av hverandre hydrogen, hydroksyl, alkyl eller alkoksy med hver gang 1-4 C-atomer, halogen, trifluormetyl eller CN og som er virksomme såvel overfor nematoder som også overfor leverigler, men på grunn av den lille oppl.øselighet i vann bare er appliserbare oralt. in which X means the group -OSO2- or -SO2O-, R means alkyl with 1 to 4 C atoms, R<1>and R" each independently means hydrogen, hydroxyl, alkyl or alkoxy with each time 1-4 C- atoms, halogen, trifluoromethyl or CN and which are effective against both nematodes and liver leeches, but due to the low solubility in water can only be applied orally.
Oppfinnelsens gjenstand er monokarboksylater av fenylguanidinsulfonsyreestere med formel: The object of the invention is monocarboxylates of phenylguanidine sulfonic acid esters with the formula:
hvori in which
X betyr-OS02- eller -S020-X means -OS02- or -S020-
R betyr hydrogen, halogen, alkyl med 1-4 C-atomer, R means hydrogen, halogen, alkyl with 1-4 C atoms,
alkoksy med 1-4 C-atomer, -CN eller -CF.,,alkoxy with 1-4 C atoms, -CN or -CF.,,
R betyr hydrogen,R means hydrogen,
eventuelt substituert alkyl,optionally substituted alkyl,
eventuelt substituert alkoksy,optionally substituted alkoxy,
eventuelt substituert alkoksyalkyl elleroptionally substituted alkoxyalkyl or
eventuelt substituert aralkyl og optionally substituted aralkyl and
2 2
R betyr hydrogen, alkyl, cykloalkyl, cykloalkyl-alkyl R means hydrogen, alkyl, cycloalkyl, cycloalkyl-alkyl
eller aralkyl, og deres fysiologisk tålbare salter med organiske eller uorganiske syrer. or aralkyl, and their physiologically tolerable salts with organic or inorganic acids.
Forbindelsene ifølge oppfinnelsen med formel I har basisk karakter. De kan anvendes som antelmintiske virksomme stoffer,som frie baser eller i form av deres salter med fysiologisk tålbare uorganiske eller organiske syrer, eksempelvis hydro-halogenider, fortrinnsvis hydroklorider, sulfater, fosfater, nitrater, maleinater, fumarater, acetater, propionater, lactater, metansulfonater eller naftalindisulfonater. The compounds according to the invention with formula I have a basic character. They can be used as anthelmintic active substances, as free bases or in the form of their salts with physiologically tolerable inorganic or organic acids, for example hydrohalides, preferably hydrochlorides, sulphates, phosphates, nitrates, maleinates, fumarates, acetates, propionates, lactates, methanesulphonates or naphthalene disulfonates.
Oppfinnelsens gjenstand er også en fremgangsmåte til fremstilling av monokarboksylater av fenylguanidinsulfonsyreestere med formel I, idet fremgangsmåten erkarakterisert vedat The object of the invention is also a process for producing monocarboxylates of phenylguanidine sulfonic acid esters with formula I, the process being characterized by
a) et substituert anilinderivat med formel IIa) a substituted aniline derivative of formula II
hvori X, R og R har den for formel I angitte betydning, omsettes in which X, R and R have the meaning given for formula I, are converted
enteneither
a-^) med et isotiourinstof f derivat med formel IIIa-^) with an isothiourea f derivative of formula III
2 3 2 3
hvori R har den til formel I angitte betydning og R betyr alkyl med 1-4 C-atomer, eller in which R has the meaning given in formula I and R means alkyl with 1-4 C atoms, or
a2^ med et O-metylisourinstoffderivat med formel Illaa2^ with an O-methylisourea derivative of formula IIIa
3 3
hvori R betyr alkyl med 1-4 Oatomer,in which R means alkyl with 1-4 O atoms,
i nærvær av et .oppløsningsmiddel og eventuelt i nærvær av en syre, eller in the presence of a solvent and optionally in the presence of an acid, or
b) et fenylguanidin-bis-karboksylat med formel IV b) a phenylguanidine biscarboxylate of formula IV
. hvori X, R og R 1 har den ovenfor angitte betydning og R 4 betyr . wherein X, R and R 1 have the above meaning and R 4 means
alkyl eller alkoksy,alkyl or alkoxy,
hydrolyseres,hydrolyzed,
og eventuelt en således dannet forbindelse med formel I, hvori R 2 betyr hydrogen alkyleres. and optionally a thus formed compound of formula I, in which R 2 means hydrogen is alkylated.
I formlene I til IV har substituentene følgende fore-trukne betydninger: R som halogen betyr fluor, klor eller brom, spesielt klor og fluor. In the formulas I to IV, the substituents have the following preferred meanings: R as halogen means fluorine, chlorine or bromine, especially chlorine and fluorine.
Alkoksy-(C^-C^) betyr metoksy, etoksy, n-propoksy, i-propoksy, n-butoksy, i-butoksy og t-butoksy, fortrinnsvis metoksy og etoksy.' Alkoxy-(C^-C^) means methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy and t-butoxy, preferably methoxy and ethoxy.'
Som eventuelt substituert alkyl R står rettlinjet^ eller forgrenet alkyl med fortrinnsvis 1-6, spesielt 1-4 C-atomer. Eksempelvis skal det nevnes eventuelt substituert metyl, etyl, As optionally substituted alkyl R is linear or branched alkyl with preferably 1-6, especially 1-4 C atoms. For example, optionally substituted methyl, ethyl,
n- og i-propyl, n-,1- og t-butyl. n- and i-propyl, n-,1- and t-butyl.
Som eventuelt substituert alkoksy R"<*>" står rettlinjet eller forgrenet alkoksy med fortrinnsvis 1 til 6, spesielt 1-4 C-atomer. Eksempelvis skal det hevnes eventuelt substituert metoksy,. etoksy, n- og i-propoksy og n-, i- og t-butoksy. As optionally substituted alkoxy R"<*>" is straight or branched alkoxy with preferably 1 to 6, especially 1 to 4 C atoms. For example, any substituted methoxy must be removed. ethoxy, n- and i-propoxy and n-, i- and t-butoxy.
som eventuelt substituert alkoksyalkyl betyr rettlinjet eller forgrenet alkoksyalkyl med fortrinnsvis 1-6, spesielt 1-4 C-atomer i alkoksydelen og fortrinnsvis 1-6, spesielt 1-4 C-atomer i alkyldelen. Eksempelvis skal det nevnes eventuelt substituert as optionally substituted alkoxyalkyl means straight or branched alkoxyalkyl with preferably 1-6, especially 1-4 C atoms in the alkoxy part and preferably 1-6, especially 1-4 C atoms in the alkyl part. For example, it must be mentioned if substituted
metoksymetyl, metoksyetyl, etoksymetyl, etoksyetyl.methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl.
R som eventuelt substituert aralkyl betyr eventueltR as optionally substituted aralkyl means optionally
i aryldelen og/eller alkyldélen substituert aralkyl med fortrinnsvis 6-10 karbonatomer i aryldelen og fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer i alkyldélen, idet alkyldélen kan være in the aryl part and/or the alkyl part substituted aralkyl with preferably 6-10 carbon atoms in the aryl part and preferably 1-4, especially 1 or 2 carbon atoms in the alkyl part, the alkyl part can be
rettlinjet eller forgrenet. Eksempelvis skål det nevnes eventuelt substituert benzyl og fenyletyl. straight or branched. For example, optionally substituted benzyl and phenylethyl are mentioned.
De forskjellige rester R kan ha en eller flere, fortrinnsvis 1-3, spesielt 1 eller 2 like eller forskjellige substituenter. Som substituenter skal det eksempelvis anføres: Alkoksy med fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer som metoksy, etoksyd, n- og i-propyloksy og n-, i- og t-butyloksy; alkyltio med fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer, som metyltio, etyltio, n- og i-propyltio og n-, i-og t-butyltio; halogenalkyl med fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer og fortrinnsvis 1-5, spesielt 1-3 halogenatomer, idet halogenatomene er like eller forskjellige, og som halogenatomer står fortrinnsvis fluor, klor eller brom, spesielt fluor som trifluormetyl; hydroksy; halogen, fortrinnsvis fluor, klor, brom og jod, spesielt fluor og klor; cyano; nitro; amino; mono-alkyl- og dialkylamino med fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer pr.alkylgruppe som metylamino, metyl-etyl-amino, The different residues R can have one or more, preferably 1-3, especially 1 or 2 identical or different substituents. As substituents, for example: Alkoxy with preferably 1-4, especially 1 or 2 carbon atoms such as methoxy, ethoxide, n- and i-propyloxy and n-, i- and t-butyloxy; alkylthio with preferably 1-4, especially 1 or 2 carbon atoms, such as methylthio, ethylthio, n- and i-propylthio and n-, i- and t-butylthio; haloalkyl with preferably 1-4, especially 1 or 2 carbon atoms and preferably 1-5, especially 1-3 halogen atoms, the halogen atoms being the same or different, and the halogen atoms are preferably fluorine, chlorine or bromine, especially fluorine as trifluoromethyl; hydroxy; halogen, preferably fluorine, chlorine, bromine and iodine, especially fluorine and chlorine; cyano; nitro; amino; mono-alkyl- and dialkylamino with preferably 1-4, especially 1 or 2 carbon atoms per alkyl group such as methylamino, methyl-ethyl-amino,
n- og i-propylamino og metyl-n-butylamino; karbalkoksy med fortrinnsvis 2-4, spesielt 2 eller karbonatomer, som karbometoksy og karboetoksy; sulfo (-SO^H); alkylsulfonyl med fortrinnsvis 1-4, spesielt.1 eller 2 karbonatomer, som metylsulfonyl og etyl-sulfohyl; arylsulfonyl med fortrinnsvis 6 eller 10 arylkarbonatomer som fenylsulfonyl. n- and i-propylamino and methyl-n-butylamino; carbalkoxy with preferably 2-4, especially 2 or carbon atoms, such as carbomethoxy and carboethoxy; sulfo (-SO^H); alkylsulfonyl with preferably 1-4, especially 1 or 2 carbon atoms, such as methylsulfonyl and ethylsulfoyl; arylsulfonyl with preferably 6 or 10 aryl carbon atoms such as phenylsulfonyl.
R 2som alkyl betyr rettlinjet eller forgrenet alkyl med fortrinnsvis 1-6, spesielt 1-4 karbonatomer. Eksempelvis skal det nevnes metyl, etyl, n- og i-propyl, n-, i- og t-butyl. R 2 as alkyl means straight or branched alkyl with preferably 1-6, especially 1-4 carbon atoms. Examples include methyl, ethyl, n- and i-propyl, n-, i- and t-butyl.
R 2 som cykloalkyl betyr mono-, bi- og tricyklisk cykloalkyl med fortrinnsvis 3-10, spesielt 3, 5 eller 6 karbonatomer. Eksempelvis skal det nevnes cyklopropyl, cyklobutyl, cyklopentyl, oyklohexyl, cykloheptyl, bicyklo[2.2.1]heptyl, bicyklo[2.2.2]octyl og adamantyl. R 2 as cycloalkyl means mono-, bi- and tricyclic cycloalkyl with preferably 3-10, especially 3, 5 or 6 carbon atoms. Examples include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, bicyclo[2.2.1]heptyl, bicyclo[2.2.2]octyl and adamantyl.
Som cykloalkylalkyl R 2 står cykloalkylalkyl med fortrinnsvis 3-10, spesielt 3/5 eller 6 karbonatomer i cykloalkyl- v delen og fortrinnsvis 1-6, spesielt 1-4 karbonatomer i alkyldélen. Cycloalkylalkyl R 2 stands for cycloalkylalkyl with preferably 3-10, especially 3/5 or 6 carbon atoms in the cycloalkyl part and preferably 1-6, especially 1-4 carbon atoms in the alkyl part.
Eksempelvis skal det nevnes cyklopropylmetyl, cyklo-pentylmetyl, cyklohexylmetyl, cyklopropyletyl, cyklopentyletyl og cyklohexyletyl. Examples include cyclopropylmethyl, cyclopentylmethyl, cyclohexylmethyl, cyclopropylethyl, cyclopentylethyl and cyclohexylethyl.
Som aralkyl R står aralkyl med fortrinnsvis 6Qlier 10, spesielt 6 karbonatomer i aryldelen og fortrinnsvis 1-4, spesielt 1 eller 2 karbonatomer i alkyldélen, idet alkyldélen kan være rettkyedet eller forgrenet. Eksempelvis skal det nevnes benzyl og fenyletyl. Aralkyl R stands for aralkyl with preferably 6 to 10, especially 6 carbon atoms in the aryl part and preferably 1-4, especially 1 or 2 carbon atoms in the alkyl part, the alkyl part can be straight-chained or branched. Examples include benzyl and phenylethyl.
Som R3-alkyl-(C^-C^) i formel III står metyl, etyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, spesielt metyl og etyl.. As R3-alkyl-(C^-C^) in formula III are methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, t-butyl, especially methyl and ethyl.
R 4 som alkyl betyr rettlinjet eller forgrenet alkyl med fortrinnsvis 1-6, spesielt 1-4 karbonatomer.. Eksempelvis skal det nevnes metyl, etyl, n- og i-propyl, n-, i- og t-butyl. R 4 as alkyl means straight or branched alkyl with preferably 1-6, especially 1-4 carbon atoms. For example, mention should be made of methyl, ethyl, n- and i-propyl, n-, i- and t-butyl.
R som alkoksy betyr rettlinjet eller forgrenet alkoksy med . fortrinnsvis 1-6, spesielt 1-4 karbonatomer. Eksempelvis skal det nevnes metyl, etoksy, n- og i-propoksy og n-, i- og t-butoksy. R as alkoxy means straight or branched alkoxy with . preferably 1-6, especially 1-4 carbon atoms. Examples include methyl, ethoxy, n- and i-propoxy and n-, i- and t-butoxy.
i Blant monokarboksylatene av fenylguanidinsulfonsyre-estere med formel I har det som antelminthica vist seg egnet de i spesiell grad hvori substituentene R betyr hydrogen, klor, trifluormetyl eller -CN, R"*" betyr hydrogen,metyl, etyl, propyl, isopropyl eller metoksymetyl og R<2>betyr hydrogen. i Among the monocarboxylates of phenylguanidine sulfonic acid esters of formula I, those in which the substituents R means hydrogen, chlorine, trifluoromethyl or -CN, R"*" means hydrogen, methyl, ethyl, propyl, isopropyl or methoxymethyl have proven to be particularly suitable as anthelmintics and R<2> is hydrogen.
De som utgangsmaterialer anvendte substituerte anilin-derivater med formel II og fenylguanidinderivatene med formel IV, samt fremgangsmåten til deres fremstilling er kjent fra DOS 2608 238. The substituted aniline derivatives of formula II and the phenylguanidine derivatives of formula IV used as starting materials, as well as the method for their preparation, are known from DOS 2608 238.
Isotiourinstoffer med formel III er delvis kjent.Isothioureas of formula III are partially known.
De kan fåes ved omsetning av eventuelt substituerte S-alkyliso-tiourinstoffer med klormaursyremetylester. They can be obtained by reacting optionally substituted S-alkylisothioureas with chloroformic acid methyl ester.
I detalj skal det eksempelvis nevnes følgende isotiourinstof f er med formel III: N-metoksykarbonyl-S-metyl-isotiourinstoff In detail, for example, the following isothioureas with formula III should be mentioned: N-methoxycarbonyl-S-methyl-isothiourea
N-metoksykarbonyl-N<1->metyl-S-metyl-isotiourinstoff N-Methoxycarbonyl-N<1->methyl-S-methyl-isothiourea
N-metoksykarbonyl-N'-etyl-S-metyl-isotiourinstoff N-methoxycarbonyl-N'-ethyl-S-methyl-isothiourea
N-metoksykarbonyl-N1-propyl-S-metyl-isotiourinstoff N-metoksykarbonyl-N'-isopropyl-S-metyl-isotiourinstoff. N-methoxycarbonyl-N1-propyl-S-methyl-isothiourea N-methoxycarbonyl-N'-isopropyl-S-methyl-isothiourea.
N-metoksykarbonyl-N'-butyl-S-metyl-isotiourinstoff N-methoxycarbonyl-N'-butyl-S-methyl-isothiourea
N-metoksykarbonyl-N'-isobutyl-S-metyl-isotiourinstoff N-metbksykarbonyl-N'-tert.butyl-S-metyl-isotiourinstoff N-metoksykarbonyl-N'-cyklohexyl-S-metyl-isotiourinstoff N-methoxycarbonyl-N'-isobutyl-S-methyl-isothiourea N-methoxycarbonyl-N'-tert-butyl-S-methyl-isothiourea N-methoxycarbonyl-N'-cyclohexyl-S-methyl-isothiourea
N-metoksykarbonyl-N'-cyklohexylmetyl-S-metyl-isotiourinstoff N-metoksykarbonyl-N<1->benzyl-S-metyl-isotiourinstoff N-methoxycarbonyl-N'-cyclohexylmethyl-S-methyl-isothiourea N-methoxycarbonyl-N<1->benzyl-S-methyl-isothiourea
N-metoksykarbonyl-N'-a-fenetyl-S-mety1-isotiourinstoff N-metoksykarbonyl-N'-3-fenetyl-S-metyl-isotiourinstoff. N-methoxycarbonyl-N'-α-phenethyl-S-methyl-isothiourea N-methoxycarbonyl-N'-3-phenethyl-S-methyl-isothiourea.
O-metylisourinstoffer med formel Illa kan fåes ved omsetning, av. tilsvarende O-alkylisourinstof f er med klormaursyremetylester. O-methylisoureas of formula Illa can be obtained by reaction, of. corresponding O-alkylisourea f is with chloroformic acid methyl ester.
Som oppløsningsmidler kommer det ved omsetning av forbindelser med formel II'" med> stoffer med formel III resp. Solvents are obtained by reacting compounds of formula II'' with> substances of formula III resp.
Illa på tale alle polare organiske oppløsningsmidler, fortrinns-Harmful to all polar organic solvents, preferably
vis alkoholer, som metanol, isopropanol, samt deres blandingershow alcohols, such as methanol, isopropanol, as well as their mixtures
med vann, ketoner, som aceton, samt deres blanding med vånn, men også etere som dioksan eller tetrahydrofuran. with water, ketones, such as acetone, as well as their mixture with water, but also ethers such as dioxane or tetrahydrofuran.
Ved fremstillingen av forbindelsene med formel il fra forbindelser med formel II med stoffer av formel III resp. Illa kan det som katalysatorer anvendes ønskelige organiske eller uorganiske syrer. Fortrinnsvis anvendér man lett tilgjengelige In the preparation of the compounds of formula II from compounds of formula II with substances of formula III or Alternatively, desirable organic or inorganic acids can be used as catalysts. Preferably use readily available ones
syre som saltsyre, svovelsyre, salpetersyre,maursyre, eddiksyre, p-toluensulfonsyre. acid such as hydrochloric acid, sulfuric acid, nitric acid, formic acid, acetic acid, p-toluenesulfonic acid.
Reaksjonstemperaturene ved fremstillingen kan vari-The reaction temperatures during production can vary
eres innen et område. Vanligvis arbeider man mellom 0°C og 120°C, fortrinnsvis mellom 10 og 30°C. Omsetningen gjennomføres vanligvis ved normaltrykk. are within an area. Generally, one works between 0°C and 120°C, preferably between 10 and 30°C. The turnover is usually carried out at normal pressure.
Omsetningen av forbindelsene med formel II med slikeThe reaction of the compounds of formula II with such
med formel III resp. Illa foregår hensiktsmessig i ekvimolare mengder. with formula III or Illa conveniently takes place in equimolar amounts.
Hydrolysene av forbindelser med formel IV gjennom-The hydrolyses of compounds of formula IV through
føres hensiktsmessig ved oppvarming i en alkohol som metanol, etanol, isopropanol samt deres blandinger med vann i nærvær av en base,f.eks. et alifatisk amin som metylamin, butylamin, piperidin eller N-metyl-piperazin, et alkoholat som natriummetylat, eller i nærvær av en uorganisk base som KOH eller NaOH. Som spesielt egnet har det vist seg oppløsninger av butylamin i metanol eller etanol. Hydrolysen lykkes også ved lengere oppvarming med vann i nærvær av et oppløsningsmiddel som aceton. is conveniently conducted by heating in an alcohol such as methanol, ethanol, isopropanol and their mixtures with water in the presence of a base, e.g. an aliphatic amine such as methylamine, butylamine, piperidine or N-methyl-piperazine, an alcoholate such as sodium methylate, or in the presence of an inorganic base such as KOH or NaOH. Solutions of butylamine in methanol or ethanol have proven to be particularly suitable. The hydrolysis is also successful by prolonged heating with water in the presence of a solvent such as acetone.
Hydrolysereaksjonens reaksjonstemperaturer kan varieres innenfor et stort område, vanligvis arbeider man mellom 0°C og 120°C, fortrinnsvis mellom 40 og 100°C. Omsetningen gjennomføres vanligvis ved normaltrykk. Den er vanligvis i basisk område av- The reaction temperatures of the hydrolysis reaction can be varied within a large range, usually working between 0°C and 120°C, preferably between 40 and 100°C. The turnover is usually carried out at normal pressure. It is usually in the basic range of
sluttet allerede etter få minutter.ended already after a few minutes.
Monokarboksylatene av fenylguanidinsulfonsyreestrene med formel I omfatter eksempelvis følgende forbindelser: N-(2-acetamido-5-fenylsulfonyloksy-fenyl)-N<1->metoksykarbonyl-guanidin The monocarboxylates of the phenylguanidine sulfonic acid esters of formula I include, for example, the following compounds: N-(2-acetamido-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-formamido-5-fenylsulfonyloksy-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-formamido-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-propionamido-5-fenylsulfonyloksy-fenyl)-N-metoksykarbonyl-guanidin N-(2-propionamido-5-phenylsulfonyloxy-phenyl)-N-methoxycarbonyl-guanidine
N-(2-butyramido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-guanidin N-(2-iso-butyramido-5-fenylsulfonyloksy-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-butyramido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine N-(2-iso-butyramido-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-valeramido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-guanidin N-(2-valeramido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine
.N-(2-iso-valeramido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbony1-guanidin .N-(2-iso-valeramido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-1-guanidine
N-(2-capronamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-guanidin N-(2-capronamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-iso-capronamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbony1-guanidin-N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-guanidin N-(2-iso-capronamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine-N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine
N- (2-acetamido-5- (4-klor-f enylsulfonyloksy) -f enyl) -N/.-metoksykarbonyl-guanidin N-(2-acetamido-5-(4-chloro-phenylsulfonyloxy)-phenyl)-N N -methoxycarbonyl-guanidine
N- (-2-acetamido-5- (3-klor-f enylsulf onyloksy) -f enyl) -N' -metoksy-karbony 1-guanid in N-(-2-acetamido-5-(3-chloro-phenylsulfonyloxy)-phenyl)-N'-methoxy-carbonyl 1-guanidine
N-(2-acetamido-5-(2-klor-fenylsulfonyloksy)-fenyl)-N'-metoksykar-bony 1-guanidin N-(2-acetamido-5-(2-chloro-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl 1-guanidine
N-(2-metoksyacetamido-5-(3-klor-fenylsulfonyloksy)-fenyl)-N'-metoksykarbony1-guanidin N-(2-methoxyacetamido-5-(3-chloro-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-brom-fenylsulfonyloksy)-fenyl)-N1 - metoksykarbony1-guanidin N-(2-methoxyacetamido-5-(3-bromo-phenylsulfonyloxy)-phenyl)-N1 - methoxycarbonyl1-guanidine
N-(2-metoksyåcetamido-5-(3-metyl-fenylsulfonyloksy)-fenyl)-N* - metoksykarbony1-guanidin N-(2-Methoxyacetamido-5-(3-methyl-phenylsulfonyloxy)-phenyl)-N*-methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-metyl-fenulsylfonyloksy)-fenyl)-N'-metoksykarbony1-guanidin N-(2-methoxyacetamido-5-(3-methyl-phenylsylphonyloxy)-phenyl)-N'-methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-tert.-butyl-fenylsulfonyloksy)-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-tert-butyl-phenylsulfonyloxy)-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-metoksy-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-methoxy-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-etoksy-fenylsulfonyloksy)-fenyl)-N'-metoksyakrbony1-guanidin N-(2-methoxyacetamido-5-(3-ethoxy-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-propoksy-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-propoxy-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-isopropoksy-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-isopropoxy-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-butoksy-fenylsulfonyloksy)-fenyl)-N1 - metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-butoxy-phenylsulfonyloxy)-phenyl)-N1-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-isobutoksy-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-isobutoxy-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(4-cyano-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(4-cyano-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-trifluormetyl-fenylsulfonyloksy)-fenyl)-N<1->metoksykarbony1-guanidin N-(2-methoxyacetamido-5-(3-trifluoromethyl-phenylsulfonyloxy)-phenyl)-N<1->methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-klor-4-metyl-fenylsulfonyloksy)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-chloro-4-methyl-phenylsulfonyloxy)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-propionamido-5-(3-trifluormetyl-fenylsulfonyloksy)-feny1-N'-metoksykarbonyl-guanidin N-(2-propionamido-5-(3-trifluoromethyl-phenylsulfonyloxy)-phenyl-N'-methoxycarbonyl-guanidine
N-(2-butyramido-5-(3-trifluormetyl-fenylsulfonyloksy)-fenyl-N'-metoksykarbonyl-guanidin N-(2-butyramido-5-(3-trifluoromethyl-phenylsulfonyloxy)-phenyl-N'-methoxycarbonyl-guanidine
N-(2-formamido-5-(3-trifluormetyl-fenylsulfonyloksy)-fenyl-N'-metoksykarbonyl-guanidin N-(2-formamido-5-(3-trifluoromethyl-phenylsulfonyloxy)-phenyl-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbo-ny 1-N "-me ty 1-guanidin N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbo-ny 1-N"-methyl 1-guanidine
N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N<1->metoksykarbo-ny 1-N "-bu ty 1-guanid in N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbo-ny 1-N "-butyl 1-guanidine
N-(2-metoksyacetamido-5-fenylsulfonyloksy-feny1)-N<1->metoksykarbo-ny 1-N" -cyklohexy 1-guanid in N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbo-ny 1-N"-cyclohexy 1-guanide in
N-(2-formamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-N"-metylguanidin N-(2-formamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-N"-methylguanidine
N-(2-propionamido-5-fenylsulfonyloksy-feny1)-N'-metoksykarbony1-N"-metylguanidin N-(2-propionamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-N"-methylguanidine
N-(2-butyramido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbony1-N"-metylguanidin N-(2-butyramido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-N"-methylguanidine
N-(2-acetamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-metylguanidin N-(2-acetamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-methylguanidine
N-(2-butyramido-5-fenoksysulfonyl-fenyl)-N<1->metoksyakrbonyl-guanidin N-(2-butyramido-5-phenoxysulfonyl-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-iso-butyramido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-guanidin N-(2-iso-butyramido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-valeramido-5-fenoksysulfonyl-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-valeramido-5-phenoxysulfonyl-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-iso-valeramido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-guanidin N-(2-iso-valeramido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-capronamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-guanidin N-(2-capronamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-iso-capronamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-guanidin N-(2-iso-capronamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N- (2-acetamido-5- (4-klor-f enoksysulf onyl) -fenyl.) -N' -metoksykarbonyl-guanidin N-(2-Methoxyacetamido-5-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine N-(2-acetamido-5-(4-chloro-phenoxysulfonyl)-phenyl.)-N'-methoxycarbonyl-guanidine
N-(2-acetamido-5-(3-klor-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-acetamido-5-(3-chloro-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-acetamido-5-(2-klor-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-acetamido-5-(2-chloro-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-klor-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-chloro-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-brom-fenoksysulfonyl)-fenyl)-N1-metoksy- . N-(2-Methoxyacetamido-5-(3-bromo-phenoxysulfonyl)-phenyl)-N1-methoxy- .
karbony1-guanidin carbonyl-guanidine
N-(2-metoksyacetamido-5-(3-metyl-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-methyl-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N, (2-metoksyacetamido-5- (3-.tert.-butyl-f enoksysulf onyl) -fenyl) -N1-me toksykarbony1-guanidin N, (2-methoxyacetamido-5-(3-tert-butyl-phenoxysulfonyl)-phenyl)-N1-me toxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-metoksy-fenoksysulfonyl)-fenyl) -N1 - metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-methoxy-phenoxysulfonyl)-phenyl)-N1-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-etbksy-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-Methoxyacetamido-5-(3-ethoxy-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-propoksy-fenoksysulfonyl)-fenyl)-N1 - metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-propoxy-phenoxysulfonyl)-phenyl)-N1-methoxycarbonyl-guanidine
N-(2-métoksyacetamido-5-(3-isopropoksy-fenoksysulf onyl)-fenyl)-N'-metoksykarbony1-guanidin N-(2-methoxyacetamido-5-(3-isopropoxy-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-1-guanidine
N-(2-metoksyacetamido-5-(3-butoksy-fenoksysulfonyl)-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-butoxy-phenoxysulfonyl)-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-metoklsyacetamido-5-(3-isobutoksy-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(3-isobutoxy-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(4-cyano-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-methoxyacetamido-5-(4-cyano-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-(3-trifluormetyl-fenoksysulfonyl)-fenyl)-N'-metoksykarbonyl-guanidin N-(2-metpksyacetamido-5-(3-klor-4-metyl-fenoksysulfonyl)-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-Methoxyacetamido-5-(3-trifluoromethyl-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine N-(2-Methoxyacetamido-5-(3-chloro-4-methyl-phenoxysulfonyl)-phenyl)- N<1->methoxycarbonyl-guanidine
N-(2-propionamido-5-(3-trifluormetyl-fenoksysulfonyl)-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-propionamido-5-(3-trifluoromethyl-phenoxysulfonyl)-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-butyramido-5-(3-trifluormetyl-fenoksysulfonyl)-fenyl)-N' - metoksykarbonyl-guanidin N-(2-butyramido-5-(3-trifluoromethyl-phenoxysulfonyl)-phenyl)-N'-methoxycarbonyl-guanidine
N-(2-formamido-5-(3-trifluormetyl-fenoksysulfonyl)-fenyl)-N<1->metoksykarbonyl-guanidin N-(2-formamido-5-(3-trifluoromethyl-phenoxysulfonyl)-phenyl)-N<1->methoxycarbonyl-guanidine
N-(2-metoksyacetamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-N"-mety1-guanidin N-(2-methoxyacetamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-N"-methyl-guanidine
N-(2-metoksyacetamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-N"-butyl-guanidin N-(2-metoksyacetamido-5-fenoksysulfonyl-fenyl)-N<1->metoksykarbonyl-N"-butyl-guanidiri N-(2-methoxyacetamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-N"-butyl-guanidine N-(2-methoxyacetamido-5-phenoxysulfonyl-phenyl)-N<1->methoxycarbonyl-N"-butyl -guanidiri
N-(2-metoksyacetamido-5-fenoksysulfonyl-fenyl)-N'-metoksykarbonyl-N"-dyklohexyl-guanidin N-(2-methoxyacetamido-5-phenoxysulfonyl-phenyl)-N'-methoxycarbonyl-N"-dichlorohexyl-guanidine
N-(2-formamido-5-fenoksysulfonyl-fenyl)-N<1->metoksykarbonyl-N"-mety1-guanidin N-(2-formamido-5-phenoxysulfonyl-phenyl)-N<1->methoxycarbonyl-N"-methyl-guanidine
N-(2-propionamido-5-fenoksysulfonyl-fenyl)-Nr<->metoksykarbony1-N"-mety1-guanidin N-(2-propionamido-5-phenoxysulfonyl-phenyl)-N<->methoxycarbonyl-N"-methyl-guanidine
N-(2-butyramido-5-fenoksysulfonyl-fenyl)-N<1->metoksykarbony1-N"-metyl-guanidin. N-(2-butyramido-5-phenoxysulfonyl-phenyl)-N<1->methoxycarbonyl-N"-methyl-guanidine.
Monokarboksylatene av fenylguanidinsulfonsyreestere med formel I i henhold til oppfinnelsen er verdifulle kjemotera-peutika og egner seg til bekjempelse av parasitære sykdommer hos mennesker og dyr, spesielt av helminter og leverigler. The monocarboxylates of phenylguanidine sulfonic acid esters of formula I according to the invention are valuable chemotherapeutics and are suitable for combating parasitic diseases in humans and animals, especially helminths and liver leeches.
De er spesielt virksomme overfor et stort antall helminter, f.eks. Haemonchus, Trichostrongylus, Ostertagia, Strongy-loides, Cooperia, Chabertia, Oesophagostomum, Hyostrongulus, Ankylostoma, Askaris og Heterakis og Fasciola. Spesielt utpreget er virkningen overfor mave-tarm-strongylider og leverigler, hvorav fremfor alt drøvtyggere angripes. Derfor anvendes forbindelsen i henhold til oppfinnelsen spesielt i veterinærmidler. They are particularly effective against a large number of helminths, e.g. Haemonchus, Trichostrongylus, Ostertagia, Strongy-loides, Cooperia, Chabertia, Oesophagostomum, Hyostrongulus, Ankylostoma, Askaris and Heterakis and Fasciola. The effect is particularly pronounced against gastrointestinal strongylids and liver leeches, of which above all ruminants are attacked. Therefore, the compound according to the invention is used especially in veterinary preparations.
Forbindelsen ifølge, oppfinnelsen med formel I kan i motsetning til de ifølge DOS 21 17 293, 22 50 911, 23 04 764 og 24 23 679 kjente forbindelser, fortrinnsvis appliseres.parenteralt og virker, i motsetning til de ifølge DOS 26 30 84 7 kjente forbihdel- ser overraskende såvel overfor nematoder som også overfor leverigler. The compound according to the invention with formula I, unlike the compounds known according to DOS 21 17 293, 22 50 911, 23 04 764 and 24 23 679, can preferably be applied parenterally and works, unlike those known according to DOS 26 30 84 7 surprisingly effective against both nematodes and liver leeches.
Forbindelsen med formel I administreres alt etter til-fellets tilstand i doseringer mellom 0,5 og.50 mg/kg legemsvekt i 1 til 14 dager. The compound of formula I is administered, depending on the condition of the case, in dosages between 0.5 and .50 mg/kg body weight for 1 to 14 days.
Til oral applikasjon kommer det på tale tabletter,, dragéer, kapsler, pulvere, granulater eller pastaer som inneholder de virksomme stoffer sammen med vanlige hjelpe- eller bærestoffer som stivelse, cellulosepulvere, talkum, magnesiumstearat, sukker, gelatin, kalsiumkarbonat, finfordelt kiselsyre, karboksymetylcellu-lose eller lignende stoffer. For oral application, oral tablets, dragees, capsules, powders, granules or pastes are available which contain the active substances together with usual auxiliary or carrier substances such as starch, cellulose powders, talc, magnesium stearate, sugar, gelatin, calcium carbonate, finely divided silicic acid, carboxymethyl cellulose -loose or similar substances.
Fremgangsmåteproduktene er ikke bare utmerket virksomme applisert oralt, men virker også parenteralt. The process products are not only excellently effective when applied orally, but also work parenterally.
Til parenteral applikasjon oppløser man enten en forbindelse med formel I i en ekvivalent av en organisk eller uorganisk syre, eller man oppløser et salt av disse forbindelser i vann. For parenteral application, either a compound of formula I is dissolved in an equivalent of an organic or inorganic acid, or a salt of these compounds is dissolved in water.
Muligheten for parenteral applikasjon av forbindelser med formel I er et betraktelig fremskritt i den antelmintiske behandling av dyr, som storfe, hester, svin, sauer, hunder, katter osv. Det er spesielt egnet for massebehandling av store dyr som storfe og hester, spesielt, når disse dyr samtidig er infisert med leverigler. The possibility of parenteral application of compounds of formula I is a considerable advance in the anthelmintic treatment of animals, such as cattle, horses, pigs, sheep, dogs, cats, etc. It is particularly suitable for mass treatment of large animals such as cattle and horses, in particular, when these animals are simultaneously infected with liver leeches.
FremstillingseksemplerManufacturing examples
FremgangsmåteApproach
Eksempel 1. 1Example 1. 1
Man oppvarmer en blanding av 3,4 g 2-metoksyacetamido-5-fenylsulfonyloksy-anilin (formel II), 25 ml metanol, 3 ,ml is-eddik og 2 g N-metoksykarbonyl-S-metyl-isotiourinstoff (formel III) en dag under tilbakeløp. Etter henstand natten over ved værelsetemperatur frafiltrerer man det utskilte N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-metoksykarbonyl-guanidin (formel I). Utbytte 0,4 g, smp. 19 0°C. A mixture of 3.4 g of 2-methoxyacetamido-5-phenylsulfonyloxy-aniline (formula II), 25 ml of methanol, 3 ml of glacial acetic acid and 2 g of N-methoxycarbonyl-S-methylisothiourea (formula III) is heated a day during reflux. After standing overnight at room temperature, the separated N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-methoxycarbonyl-guanidine (formula I) is filtered off. Yield 0.4 g, m.p. 19 0°C.
På analog måte vil man av substituerte 2-acylamino-anilinderivater (formel II) og N-substituerte N-metoksykarbonyl-S-metyl-isotiourinstoffer (formel III) få: 1.2 N-(2-formamido-5-fenylsulfonyloksy-fenyl)-N'-metyl-N"-metoksykarbonyl-guanidin In an analogous way, from substituted 2-acylamino-aniline derivatives (formula II) and N-substituted N-methoxycarbonyl-S-methyl-isothioureas (formula III) you get: 1.2 N-(2-formamido-5-phenylsulfonyloxy-phenyl)- N'-methyl-N"-methoxycarbonyl-guanidine
1.3. N-(2-acetamido-5-fenylsulfonyloksy-fenyl)-N'-mety1-N"-metoksykarbonyl-guanidin 1.3. N-(2-acetamido-5-phenylsulfonyloxy-phenyl)-N'-methyl-N"-methoxycarbonyl-guanidine
1.4 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N<1->1.4 N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N<1->
mety1-N"-metoksykarbony1-guanidinmethyl-N"-methoxycarbonyl-guanidine
1.5 N-(2-propionamido-5-fenylsulfonyloksy-fenyl)-N'-mety1-N"-metoksykarbonyl-guanidin 1.5 N-(2-propionamido-5-phenylsulfonyloxy-phenyl)-N'-methyl-N"-methoxycarbonyl-guanidine
1.6 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-etyl-N"-metoksykarbonyl-guanidin 1.6 N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-ethyl-N"-methoxycarbonyl-guanidine
1.7. N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N\-propyl-N"-metoksykarbonyl-guanidin 1.7. N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N\-propyl-N"-methoxycarbonyl-guanidine
1.8 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-buty1-N"-metoksykarbonyl-guanidin 1.8 N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-buty1-N"-methoxycarbonyl-guanidine
1.9<;>N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-isobuty1-N"-metoksykarbony1-guanidin 1.9<;>N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-isobuty1-N"-methoxycarbonyl1-guanidine
1.10 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N<1->1.10 N-(2-Methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N<1->
cyklohexyl-N"-metoksykarbonyl-guanidincyclohexyl-N"-methoxycarbonyl-guanidine
1.11 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-cyklohexyImety1-N"-metoksykarbony1-guanidin 1.12 N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-benzy1-N"-metoksykarbony1-guanidin 1.11 N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-cyclohexylmethyl-N"-methoxycarbonyl-1-guanidine 1.12 N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-benzyl-N"-methoxycarbonyl -guanidine
Fremgangsmåte a2)Procedure a2)
Eksempel 2Example 2
Man oppvarmer en blanding av 3,4 g 2-metoksyacetamido-5-fenylsulfonyloksy-anilin (formel II),, 2,5 ml metanol, 3 ml is-éddik og 2 g.N-metoksykarbonyl-O-metyl-isourinstoff (formel Illa) en dag under tilbakeløp. Etter henstand natten over ved værelsetemperatur frafiltrerer man væsken fra de utskilte forurensninger, inndamper filtratet til tørrhet, opptar residuet i eddikester, vasker flere ganger med vann og inndamper oppløsningsmidlet etter tørking med MgSO^under nedsatt trykk. Etter utrøring av residuet med 0,5 n HCl ved værelsetemperatur og utfelling av filtratet med ammoniakk fåes det dannede N-(2-metoksyacetamido-5-fenyloksy-fenyl)-N'-metoksykarbonyl-guanidin (formel I) i ren form. Det er etter tynnsjiktskromatografien identsik med det ifølge Eks. 1 dannede fremgangsmåte-produkt. A mixture of 3.4 g of 2-methoxyacetamido-5-phenylsulfonyloxy-aniline (formula II), 2.5 ml of methanol, 3 ml of glacial acetic acid and 2 g of N-methoxycarbonyl-O-methylisourea (formula Illa) is heated. a day during reflux. After standing overnight at room temperature, the liquid is filtered off from the separated impurities, the filtrate is evaporated to dryness, the residue is taken up in vinegar, washed several times with water and the solvent is evaporated after drying with MgSO4 under reduced pressure. After stirring the residue with 0.5 n HCl at room temperature and precipitation of the filtrate with ammonia, the formed N-(2-methoxyacetamido-5-phenyloxy-phenyl)-N'-methoxycarbonyl-guanidine (formula I) is obtained in pure form. According to the thin-layer chromatography, it is identical to that according to Ex. 1 formed method-product.
Fremstilling av utgangsmaterialet med formel Illa:Preparation of the starting material with formula Illa:
Man oppløser 246 g O-metyl-isourinstoffsulfat i 300 ml vann og tildrypper ved 10°C 163 ml klormaursyremetylester og deretter 170 g NaOH, oppløst i 510 ml vann. Man omrører ytterligere 3 timer ved værelsetemperatur. Deretter ekstraherer man reaksjons-, oppløsningen med eddikester og tørker dette ekstrakt med vannfritt natriumsulfat. Etter inndampning under nedsatt trykk ved en Dissolve 246 g of O-methylisourea sulfate in 300 ml of water and add dropwise at 10°C 163 ml of chloroformate methyl ester and then 170 g of NaOH, dissolved in 510 ml of water. Stir for a further 3 hours at room temperature. The reaction solution is then extracted with acetic acid and this extract is dried with anhydrous sodium sulphate. After evaporation under reduced pressure at a
maksimal badtemperatur på 40°C får man N-metoksykarbonyl-O-metyl-isourinstoff som olje, som etterhvert stivner til krystaller med et smeltepunkt på 4 0°C. Utbytte 150 g. maximum bath temperature of 40°C, N-methoxycarbonyl-O-methyl-isourea is obtained as an oil, which eventually solidifies into crystals with a melting point of 40°C. Yield 150 g.
Fremgangsmåte b) (Hydrolyse)Method b) (Hydrolysis)
Eksempel 3Example 3
Man omrører en blanding av 2 g N-(2-metoksyacetamido-5-fenylsulfonyloksyfenyl)-N<1>,N"-bis-metoksykarbonylguanidin (formel IV), 20 ml metanol og 2ml butylamin i 10 minutter ved 50°C. Allerede etter to minutter er det dannet en klar oppløsning, hvorav det-kort deretter faller ut N-(2-metoksyacetamido-5-fenylsulfonyl-oksy-f enyl)-N1-metoksykarbonyl-guanidin (formel I).. Man lar reaksjonsb landingen stå noen timer ved 10°C, frafiltrerer ut-fellingen og vasker den med metanol. Utbytte 1,7 g, smp. 190°C under spaltning. Fremgangsmåteproduktet er identisk med det som fåes ifølge Eks. 1. A mixture of 2 g of N-(2-methoxyacetamido-5-phenylsulfonyloxyphenyl)-N<1>,N"-bis-methoxycarbonylguanidine (formula IV), 20 ml of methanol and 2 ml of butylamine is stirred for 10 minutes at 50°C. Already after two minutes, a clear solution is formed, from which N-(2-methoxyacetamido-5-phenylsulfonyl-oxy-phenyl)-N1-methoxycarbonyl-guanidine (formula I) precipitates shortly afterwards. The reaction mixture is allowed to stand a few hours at 10° C., filter off the precipitate and wash it with methanol. Yield 1.7 g, m.p. 190° C. during cleavage. The process product is identical to that obtained according to Example 1.
Det for gjennomføring av reaksjonen nødvendige N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N'-N"-bis-metoksykarbonyl-guanidin (formel IV) fåes ifølge. DOS 26 08 .238 The N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N'-N"-bis-methoxycarbonyl-guanidine (formula IV) required for carrying out the reaction is obtained according to. DOS 26 08 .238
Eks. 5.2.Ex. 5.2.
I stedet for butylamin kan man ved samme arbeidsteknikk også anvende en 40%-ig vandig metylaminoppløsning, piperidin eller N-metyl-piperazin. Tilsvarende resultater fåes også med natrpn-lut, ammoniakk eller natriummetylat i alkoholisk oppløsning. Instead of butylamine, a 40% aqueous methylamine solution, piperidine or N-methyl-piperazine can also be used with the same working technique. Similar results are also obtained with caustic soda, ammonia or sodium methylate in alcoholic solution.
Eksempel 4 (dessuten fremgangsmåte b) )Example 4 (also method b) )
Analogt Eks. 3 fremstilles de i følgende tabell opp-førte forbindelser med formel I fra de tilsvarende utgangsmaterialer Analog Ex. 3, the compounds of formula I listed in the following table are prepared from the corresponding starting materials
4 4
med formel IV, hvori X hver gang betyr -SO2O- og R -OCH^: with formula IV, in which X each time means -SO2O- and R -OCH^:
Eksempel 5 (dessuten fremgangsmåte b)) Example 5 (also method b))
Analogt Eks. 3 fremstilles de i følgende tabell opp-stilte forbindelser med formel I fra de tilsvarende utgangsmaterialer med formel IV, hvori X hver gang betyr -0-S09- og 4 z Analog Ex. 3, the compounds of formula I listed in the following table are prepared from the corresponding starting materials of formula IV, in which X each time means -O-S09- and 4 z
R betyr -0CH3:R stands for -0CH3:
Det for fremstilling av fremgangsmåteproduktet ifølge Eks. 3.36 nødvendige N-(2-acetamido-5-(3-trifluormetyl-fenylsulfonyloksy)-fenyl-N',N"-bis-metoksykarbonylguanidin (formel IV) med smp. 152°C fåes tilsvarende Eks.■3-i DOS 26 08 238 av 2-nitro-4-(3-trifluormetyl-fenoksysulfonyl)-klorbenzol med smp. 65°C over 2-nitro-4-(3-trifluormetyl-fenoksysulfonyl)-anilin med smp. 130°C, 2-nitro-4-(3-trifluormetyl-fenoksysulfonyl)-anilin med smp. 130°C og 2-nitro-4-(3-trifluormetyl-fenoksysulfonyl)-acetanilid med smp. 114°C, samt 2-amino-4-(3-trifluormetyl-fenoksy-sulf onyl) -acetanilid med smp. 141°C. For the production of the process product according to Ex. 3.36 required N-(2-acetamido-5-(3-trifluoromethyl-phenylsulfonyloxy)-phenyl-N',N"-bis-methoxycarbonylguanidine (formula IV) with m.p. 152°C is obtained corresponding to Ex.■3-in DOS 26 08 238 of 2-nitro-4-(3-trifluoromethyl-phenoxysulfonyl)-chlorobenzene with m.p. 65°C over 2-nitro-4-(3-trifluoromethyl-phenoxysulfonyl)-aniline with m.p. 130°C, 2-nitro -4-(3-trifluoromethyl-phenoxysulfonyl)-aniline with a melting point of 130°C and 2-nitro-4-(3-trifluoromethyl-phenoxysulfonyl)-acetanilide with a melting point of 114°C, as well as 2-amino-4-(3 -trifluoromethyl-phenoxy-sulfonyl)-acetanilide with mp 141°C.
Eksempel 6 (fremgangsmåte b))Example 6 (method b))
Man oppvarmer 2,5 g N-(2-metoksyacetamido-5-fenyl-sulf onyloksy-f enyl) -N ' ,N"-bis-metoksykarbonyl.guanidin (formel IV) 2.5 g of N-(2-methoxyacetamido-5-phenyl-sulfonyloxy-phenyl)-N',N"-bis-methoxycarbonylguanidine (formula IV) are heated
i 25. ml aceton og 25 ml vann i 24 timer i autoklav ved 90°C.in 25 ml of acetone and 25 ml of water for 24 hours in an autoclave at 90°C.
Etter avkjøling frafiltrerer man råproduktet. Det utrøres for rensing flere ganger i 25 ml 0/5 n HC1 ved værelsetemperatur, frafiltreres hver.gang fra uoppløst og filtratet blandes med ammoniakk. Etter filtrering og tørking av residuet får man 0,5 g rent N-(2-metoks<y>acetamido-5-fen<y>lsulfon<y>loksy-fen<y>l)rN<1->metoksykarbonyl-guanidin med smp. 190°C (under spaltning), After cooling, the crude product is filtered off. For purification, it is stirred several times in 25 ml of 0/5 n HC1 at room temperature, each time the undissolved material is filtered off and the filtrate is mixed with ammonia. After filtering and drying the residue, 0.5 g of pure N-(2-methoxy<y>acetamido-5-phen<y>lsulfon<y>oxy-phen<y>l)rN<1->methoxycarbonyl-guanidine is obtained with m.p. 190°C (during decomposition),
hvilket er identisk med fremgangsmåteproduktet fra Eks. 1. which is identical to the process product from Ex. 1.
Eksempel 7 (Saltdannelse)Example 7 (Salt formation)
Man utrører 24 g av det ifølge Eks. 1 dannede frie N-(2-metoksyacetamino-5-fenylsulfonyloksy-fenyl)-N<1->metoksykarbonyl-guanidin i 250 ml metanol og gjør det kongosurt med alkoholisk klorhydrogenoppløsning. Derpå inndampes oppløsningen til tørr- One stirs 24 g of it according to Ex. 1 formed free N-(2-methoxyacetamino-5-phenylsulfonyloxy-phenyl)-N<1->methoxycarbonyl-guanidine in 250 ml of methanol and makes it congo acid with alcoholic hydrogen chloride solution. The solution is then evaporated to dryness
het under nedsatt trykk, residuet blandes med eter og hydroklori-hot under reduced pressure, the residue is mixed with ether and hydrochloric
det av N-(2-metoksyacetamido-5-fenylsulfonyloksy-fenyl)-N1-metoksykarbonyl-guanidin frafiltreres. Etter vasking med eter og tørking under nedsatt trykk over etsnatron utgjør utbyttet 25 g. of N-(2-methoxyacetamido-5-phenylsulfonyloxy-phenyl)-N1-methoxycarbonyl-guanidine is filtered off. After washing with ether and drying under reduced pressure over caustic soda, the yield is 25 g.
Analogt fåes hydrokloridéne av de øvrige fremgangs-måteprodukter slik de omtales i Eks. 2-6. Analogously, the hydrochlorides are obtained from the other process products as described in Ex. 2-6.
Claims (5)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19782836385 DE2836385A1 (en) | 1978-08-19 | 1978-08-19 | MONOCARBOXYLATES OF PHENYLGUANIDINE SULPHONIC ACID ESTERS, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINAL PRODUCTS |
Publications (1)
Publication Number | Publication Date |
---|---|
NO792696L true NO792696L (en) | 1979-02-20 |
Family
ID=6047464
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO792696A NO792696L (en) | 1978-08-19 | 1979-08-17 | MENOCARBOXYLATES OF PHENYLGUANIDIC ACID ESTERS AND PROCEDURES FOR THEIR PREPARATION |
Country Status (13)
Country | Link |
---|---|
US (1) | US4254143A (en) |
EP (1) | EP0008438A1 (en) |
JP (1) | JPS5531083A (en) |
AU (1) | AU5003679A (en) |
DE (1) | DE2836385A1 (en) |
DK (1) | DK344379A (en) |
ES (2) | ES483350A1 (en) |
FI (1) | FI792548A (en) |
IL (1) | IL58066A0 (en) |
NO (1) | NO792696L (en) |
NZ (1) | NZ191336A (en) |
PT (1) | PT70076A (en) |
ZA (1) | ZA794355B (en) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4348406A (en) | 1980-10-20 | 1982-09-07 | Schering Corporation | Novel guanidine derivatives |
DE3232959A1 (en) * | 1982-09-04 | 1984-03-08 | Hoechst Ag, 6230 Frankfurt | SUBSTITUTED Benzenesulfonic Acid Ester, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS MEDICINAL PRODUCTS |
DE3412939A1 (en) * | 1984-04-06 | 1985-10-17 | Behringwerke Ag, 3550 Marburg | SUBSTRATES FOR HYDROLASES, METHOD FOR THEIR PRODUCTION AND THEIR USE |
JPH0825731B2 (en) * | 1990-09-20 | 1996-03-13 | 信越化学工業株式会社 | Method for producing rare earth phosphate |
CN103848761B (en) * | 2014-03-19 | 2016-03-23 | 连云港市亚晖医药化工有限公司 | The preparation of O-methyl-isourea methyl-formiate |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4024176A (en) * | 1974-05-15 | 1977-05-17 | Bayer Aktiengesellschaft | Substituted phenylguanidines and processes for their preparation and use |
US4088780A (en) * | 1974-05-15 | 1978-05-09 | Bayer Aktiengesellschaft | Substituted phenylguanidines and processes for their preparation and use |
DE2441201C2 (en) * | 1974-08-28 | 1986-08-07 | Hoechst Ag, 6230 Frankfurt | 2-Carbalkoxyamino-5 (6) -phenyl-sulfonyloxy-benzimidazoles and process for their preparation |
DE2441202C2 (en) * | 1974-08-28 | 1986-05-28 | Hoechst Ag, 6230 Frankfurt | 2-Carbalkoxyamino-benzimidazolyl-5 (6) -sulfonic acid-phenyl ester, process for their preparation and anthelmintic compositions containing them |
DE2608238A1 (en) * | 1976-02-28 | 1977-09-08 | Hoechst Ag | SUBSTITUTED PHENYLGUANIDINE AND THE METHOD OF MANUFACTURING THEREOF |
DE2609994A1 (en) * | 1976-03-10 | 1977-09-15 | Bayer Ag | 2-FORMYLAMINO-PHENYLGUANIDINE, THE METHOD FOR THEIR MANUFACTURING AND THEIR USE AS A MEDICINAL PRODUCT |
-
1978
- 1978-08-19 DE DE19782836385 patent/DE2836385A1/en not_active Withdrawn
-
1979
- 1979-08-13 ES ES483350A patent/ES483350A1/en not_active Expired
- 1979-08-13 ES ES483349A patent/ES483349A1/en not_active Expired
- 1979-08-16 EP EP79102980A patent/EP0008438A1/en not_active Withdrawn
- 1979-08-16 US US06/068,532 patent/US4254143A/en not_active Expired - Lifetime
- 1979-08-16 FI FI792548A patent/FI792548A/en not_active Application Discontinuation
- 1979-08-17 DK DK344379A patent/DK344379A/en unknown
- 1979-08-17 IL IL58066A patent/IL58066A0/en unknown
- 1979-08-17 NZ NZ191336A patent/NZ191336A/en unknown
- 1979-08-17 ZA ZA00794355A patent/ZA794355B/en unknown
- 1979-08-17 PT PT70076A patent/PT70076A/en unknown
- 1979-08-17 NO NO792696A patent/NO792696L/en unknown
- 1979-08-17 AU AU50036/79A patent/AU5003679A/en not_active Abandoned
- 1979-08-18 JP JP10453679A patent/JPS5531083A/en active Pending
Also Published As
Publication number | Publication date |
---|---|
US4254143A (en) | 1981-03-03 |
ZA794355B (en) | 1980-08-27 |
DK344379A (en) | 1980-02-20 |
DE2836385A1 (en) | 1980-03-06 |
ES483350A1 (en) | 1980-04-16 |
IL58066A0 (en) | 1979-12-30 |
NZ191336A (en) | 1981-01-23 |
AU5003679A (en) | 1980-02-28 |
EP0008438A1 (en) | 1980-03-05 |
FI792548A (en) | 1980-02-20 |
ES483349A1 (en) | 1980-04-16 |
PT70076A (en) | 1979-09-01 |
JPS5531083A (en) | 1980-03-05 |
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